Transforming Growth Factor-beta is a Possible Paracrine Mediator in the Human Endometrial Decidualization / 대한불임학회지

ABSTRACT

OBJECTIVES: To investigate the role of TGF (Transforming growth factor-beta) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. DESiGN: in the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-beta1 are added. METHODS: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELiSA) and immunohistochemical staining are utilized to detect proteins in the tissue. RESULTS: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-beta1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-beta1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4,325 pg/ml in E2-dominant and 2,000 pg/ml in P4-dominant condition compare to 150 pg/ ml in no hormone. in separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-beta and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. CONCLUSION: it is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-beta and HGF are two possible paracrine mediators in the human endometrial decidualization.